PB2087: EFFICACY OF A 3RD COVID VACCINE, INCLUDING DURING A BTKI PAUSE, IN INDIVIDUALS WITH WALDENSTRÖM MACROGLOBULINEMIA AND FOLLICULAR LYMPHOMA
Authors: K. Rankin, B. Beaton, S. Sasson, J. Raedemaecker, A. Wong, P. Hastak, C. Phetsouphanh, A. Warden, M. Patel, V. Klemm, C. M. L. Munier, A. Carey Hoppe, F. Tea, A. Pillay, A. Ospina, A. Aggarwal, O. Lavee, I. D. Caterson, S. Turville, A. D. Kelleher, F. Brilot, J. Trotman
Journal: HemaSphere (2022)

Background: Patients (pts) with indolent lymphomas are at increased risk of severe COVID-19 infection. We have shown limited seroconversion and live viral neutralisation (VN), but preserved COVID-specific T cell responses after 2 doses of mRNA COVID-19 vaccination in such pts. (Beaton, B ASH 2021, 149348). A 3rd vaccine dose to complete primary vaccination has since been recommended. Aims: To assess humoral & cellular immune responses to a 3rd COVID-19 (mRNA) vaccination in pts with follicular lymphoma (FL) & Waldenström Macroglobulinemia (WM), including assessment of response after pausing BTKi therapy in WM pts. Methods: Patients with WM, FL & healthy controls (HC) were enrolled in a prospective observational study to measure immune responses 21-28 days after a 3rd mRNA COVID-19 vaccine. Immune response was measured by mean fluorescence intensity (MFI) of anti-SARS-CoV-2 spike antibodies (ASAb) obtained using a high-sensitivity live cell assay, live VN to a panel of SARS-CoV-2 variants of concern, and CD4+ & CD8+ antigen-specific T cell responses. The associated TRIBECA (TReatment Interruption of BTKi to Enhance COVID-19 Antibody response) study sought to determine if a superior immune response could be gained by pause of BTKi therapy prior to and up to 4 weeks after 3rd vaccine dose. Patients were closely monitored during the BTKi pause with weekly clinical, full blood count and IgM assessments. WM pts receiving a 3rd dose while continuing on BTKi served as a control. Statistical analysis of medians between cohorts were compared by the non-parametric Mann-Whitney (Graphpad Prism). Comparison of medians between paired grouped data was assessed by 2-way ANOVA. Results: To date, 56 of 125 pts had their ASAb measured following 3rd vaccine dose administered between October 2021 and January 2022: 28 WM pts (including 6/9 WM pts on the BTKi pause sub-study), 24 FL pts and 4 HC. Median age was 68 years with 21 females and 35 males. Median follow up from 2nd dose was 140 days (range: 79-170 days). In antibody responders, median MFI fell from 163042 (IQR 82663-249934) 28 days post 2nd dose to 52117 (IQR 19942-60973) (p<0.0001) immediately before the 3rd dose. Median MFI in all FL & WM pts pre- 3rd dose vaccine was 17111 (IQR 0-52650), rising significantly post 3rd dose to a median of 86730 (IQR 0-221937). Only 4/20 pts without measurable ASAb prior to the 3rd dose (2 WM, 2 FL) developed measurable ASAb following the 3rd dose: 16/20 patients (8 WM, 8FL, all treated) had no ASAb response. The median MFI in pts who underwent a BTKi treatment pause rose from 9151 (IQR 1671-21232) pre-3rd dose to 87720 (IQR 2785-152195) post 3rd dose, significantly higher than the median MFI in WM pts who did not pause their BTKi, which rose from 16769 (IQR 218-22447) pre- to 20252 (IQR 168-114262) post 3rd dose, (p = 0.016). Of the 5/125 with COVID infection in the study to date, only one patient (without measurable ASAb) in this 3-dose cohort had COVID, requiring intensive care support. Summary/Conclusion: Most WM & FL pts who responded to a 2nd dose COVID vaccine showed a decline in ASAb titre over time which increased following a 3rd mRNA vaccine. Only 20% of pts without detectable ASAb pre-3rd dose showed improvement post 3rd dose, highlighting the importance of other COVID protection strategies in these pts. Although initial numbers are small, there may be a higher increment in ASAb when BTKi therapy is paused around the time of vaccination. Comprehensive immune analysis, including VN and T-cell response on the entire FL & WM cohort will be presented at the EHA congress.